FDA Expands Use of HCV Drug Daclatasvir (Daklinza )

Megan Brooks

February 09, 2016

The US Food and Drug Administration (FDA) has approved expanded use of the NS5A replication complex inhibitor daclatasvir (Daklinza, Bristol-Myers Squibb) for hepatitis C virus (HCV) infection.

The drug can now be used in combination with sofosbuvir (Sovaldi, Gilead Sciences), with or without ribavirin, to treat patients with HCV genotypes 1 and 3, the company said in a news release.

The FDA first approved daclatasvir for treatment of chronic HCV genotype 3 in July 2015, as reported by Medscape Medical News.

"The expanded indication for Daklinza offers an additional treatment option for multiple subsets of patients who have genotype 1 or 3 chronic HCV," Chris Boerner, head of US Commercial, Bristol-Myers Squibb, said in a company news release.

The expanded label includes three additional "challenging-to-treat" patient populations — those with HCV and HIV-1 coinfection, advanced cirrhosis, or recurrence of HCV after liver transplant, the release notes. "HCV/HIV-coinfected patients and patients with advanced cirrhosis or post-transplant recurrence of HCV still pose a treatment challenge to physicians," Boerner added.

The efficacy and safety of daclatasvir-containing regimens were demonstrated in the ALLY-1 and ALLY-2 phase 3 clinical trials.

The ALLY-2 trial included 153 treatment-naïve and treatment-experienced HCV/HIV-coinfected patients treated with daclatasvir plus sofosbuvir for 12 weeks. The primary endpoint was sustained virologic response at week 12 (SVR12) in genotype 1 treatment-naïve patients.

SVR12 rates were "high" regardless of baseline subgroup, including Black/African American (98% in all genotypes studied), and high baseline viral load (≥ 6,000,000 IU/mL) (97% in all genotypes studied), the company said.

SVR12 rates were also similar in patients on highly active antiretroviral therapy (HAART) regimens, which included protease inhibitors (97% in all genotypes), non-nucleoside reverse transcriptase inhibitors (100% in all genotypes), and integrase inhibitors (95% in all genotypes), they point out.

There were no treatment-related serious adverse events, and no patient discontinued treatment due to adverse events (AEs). The most common treatment-related AEs were fatigue (15%), nausea (9%), headache (8%), and diarrhea (7%).

The ALLY-1 trial included 113 patients with chronic HCV infection and Child-Pugh A, B, or C advanced cirrhosis or HCV recurrence after liver transplant treated with daclatasvir plus sofosbuvir with ribavirin for 12 weeks. SVR12 rates were similar between genotype 3 (5/6 with Child-Pugh B or C cirrhosis and 10/11 post-liver transplant) and genotype 1 subjects with or without decompensated cirrhosis, the company said.

The ALLY-1 and ALLY-2 trials showed that daclatasvir can be given alongside the most commonly used HIV medications and post-transplant immunosuppressive regimens, the company noted in their news release.

"Based on the drug-drug interaction profile, there is no need to change or adjust HAART regimens, including darunavir-ritonavir, atazanavir-ritonavir, lopinavir-ritonavir, efavirenz, raltegravir, dolutegravir, nevirapine and rilpivirine," they point out. "The dose of Daklinza was adjusted for some HAART regimens. Daklinza is also compatible with many immunosuppressive regimens, with no treatment-limiting drug-drug interactions. The ALLY-1 trial studied most immunosuppressants: cyclosporine, tacrolimus, sirolimus, everolimus, corticosteroids, or mycophenolate mofetil."

Full prescribing information for daclatasvir is available here.

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